Morgan and colleagues [1] evaluated folate supplementation during methotrexate therapy for rheumatoid arthritis. It is encouraging to see evidence that such supplementation can reduce the severity of common side effects related to methotrexate therapy. Some questions remain, however, regarding the study design, the conclusions, and the recommendations.

First, patients in the high-dose arm of the study reportedly received 27.5 mg of folic acid per week (or approximately 5 mg/d as reported); however, previous interim reports of what I believe to be the same study stated that patients assigned to this arm received 50 mg weekly (10 mg/d for 5 days) [2, 3]. Why was the dose changed? Were problems associated with the original dose, and, if the dose was changed after initiation of the study, how did that affect the blinding?